Activity of Anlotinib in the Second-Line Therapy of Metastatic Gastrointestinal Stromal Tumors: A Prospective, Multicenter, In Vitro Study.

Yongjian Zhou, Chunling Zeng, Xiaofeng Sun, Jun Zhang, Hongyan Qu, Xinhua Zhang, Ye Zhou, Zimin Liu, Xiaojun Wu, Xin Wu, Xuelong Jiao, Lin Shen, Yanbing Zhou, Yuexiang Wang, Jian Li

Journal: The oncologist 2023;28(4):e191-e197

PMID: 36779523

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Abstract

BACKGROUND

Anlotinib is a multi-target tyrosine kinase inhibitor that can effectively inhibit tumor cell proliferation after receptor kinase activation caused by KIT gene mutation.

METHODS

We tested the inhibitory effect of anlotinib in GIST cell lines with different gene mutations and evaluated the efficacy of anlotinib for patients with metastatic GIST after imatinib failure in a multicenter, single-arm, phase II study.

RESULTS

In vitro, V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib. Moreover, anlotinib was able to partly suppress the activation loop mutation D820A from exon 17 while another activation loop mutation N822K, also from exon 17, was resistant to anlotinib. From September 2018 to October 2020, 64 patients from 9 Chinese medical centers were enrolled in this study. Seven patients had partial response and 39 patients had stable disease. The median PFS was 8.0 months. There was no statistical significance comparing with PFS of sunitinib second-line therapy at the same period. The most common adverse events related to anlotinib treatment were hypertension, neutropenia, and fatigue.

CONCLUSION

Anlotinib showed moderate antitumor activity in drug-resistant GIST cell lines in vitro, and good PFS and better tolerance in second-line therapy study.

Address: Department of Gastric Surgery, Fujian Medical University Union Hospital, Fujian, People's Republic of China.; CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.; Department of Internal Medicine, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & the Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu, People's Republic of China.; Department of Gastrointestinal Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.; The Second Ward of Gastroenterology Department, Harbin Medical University Cancer Hospital, Heilongjiang, People's Republic of China.; Department of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangdong, People's Republic of China.; Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.; Department of Oncology, the Affiliated Hospital of Qingdao University, Shandong, People's Republic of China.; Department of Colorectal Surgery, State Key Laboratory of Oncology in South People's Republic of China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.; Department of General Surgery, the General Hospital of the People's Liberation Army, Beijing, People's Republic of China.; Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Shandong, People's Republic of China.; Department of GI Oncology, Laboratory of Carcinogenesis and Translational Research of the Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, People's Republic of China.

DOI: 10.1093/oncolo/oyac271

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MeSH Terms: Humans, Gastrointestinal Stromal Tumors, Antineoplastic Agents, Prospective Studies, Sunitinib, Mutation, Proto-Oncogene Proteins c-kit, Drug Resistance, Neoplasm